Pentamidine inhibits proliferation, migration and invasion in endometrial cancer via the PI3K/AKT signaling pathway

• Published in: BMC women's health Vol. 22; no. 1; p. 470
• Main Authors: Lin, Lin, Gao, Yunan, Hu, Xiaochen, Ouyang, Jiabao, Liu, Chunbo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.11.2022; BioMed Central; BMC
• Subjects: Breast cancer; Cancer therapies; Cell culture; Cell cycle; Cell growth; Cell Proliferation; Chemotherapy; Dosage and administration; Drug dosages; Drug therapy; Endometrial cancer; Endometrial Neoplasms - pathology; Female; Gynecology; Humans; Kinases; LY294002; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase 9 - therapeutic use; Medical prognosis; Melanoma; Mitochondrial DNA; Patient outcomes; Pentamidine; Pentamidine - pharmacology; Pentamidine - therapeutic use; Pentamidine isethionate; Phosphatidylinositol 3-Kinases - metabolism; Phosphatidylinositol 3-Kinases - therapeutic use; PI3K/AKT pathway; Prostate; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Statistical analysis; Tumors; Womens health; China; United States > US; Pentamidine; LY294002; Endometrial cancer; PI3K/AKT pathway
• ISSN: 1472-6874; 1472-6874
• DOI: 10.1186/s12905-022-02078-1

Pentamidine has been reported to have many pharmacological effects including anti- protozoal, anti-inflammatory, and anti-tumor activities. The aim of this study is to investigate the potential therapeutic role of Pentamidine and molecular mechanisms of Pentamidine on PI3K/AKT signaling pathway underlying the anti-tumor properties in endometrial cancer. Our study was carried out in the central laboratory of Harbin Medical University from 2019 to 2021. Human endometrial cancer cell lines Ishikawa and HEC-1A were treated with Pentamidine. The proliferation ability of cells was investigated by MTS and colony formation assays. The cell cycle distribution was detected by flow cytometry. Cell migration and invasion were analyzed by using the wound healing assay and Transwell assay. Western blotting was performed to measure the levels of AKT, p-AKT, MMP-2, and MMP-9. Our results revealed that treatment of Pentamidine inhibited proliferation, migration and invasion of Ishikawa and HEC-1A endometrial cancer cells. Mechanistic investigation showed that Pentamidine inhibited PI3K/AKT signaling pathway and also reduced the expression of MMP-2 and MMP-9. In addition, co-treatment with PI3K kinase inhibitor LY294002 and Pentamidine leaded to increased repression of cell viability and the protein expression of p-AKT in Ishikawa cells. Pentamidine suppresses PI3K/AKT signaling pathway, and inhibits proliferation, migration and invasion of EC cells. These findings suggested that Pentamidine might be a potential candidate for treating EC through PI3K/AKT pathway.